Fragile X syndrome (FXS) is the most common known inherited cause of mental retardation, but it can also manifest as a broad spectrum of behavior and learning problems in individuals with an IQ in the normal range. This genotype-phenotype study assesses in detail neurocognitive abilities, emotional status, and physical features in individuals with the premutation and in individuals with the full mutation. This information is correlated with molecular measures, including the overall CGG repeat number of the FMR1 gene, the degree of methylation, the messenger RNA levels, and the FMR1 protein (FMRP) levels. In addition, in females the activation ratio (AR) which measures the percentage of cells that have the normal FMR1 gene on the active X chromosome is also assessed. This study is carried out at two centers: Denver, Colorado and Melbourne, Australia. In Australia, the expertise of Drs. Danuta Loesch and Richard Huggins include a quantitative pedigree assessment that will give us insight to how background genetic effects modify the fragile X phenotype. We are particularly interested in whether clinical involvement truly exists in individuals with the premutation.